Macrophage-centered immune-fibrotic persistence in endometriosis and adenomyosis: non-hormonal immunopharmacological targets

Endometriosis and adenomyosis are commonly managed through endocrine suppression, analgesia and surgery, yet these approaches do not fully explain persistent pain, recurrence, fibrotic remodeling or variable treatment response. A growing body of immune and single-cell evidence supports a complementary view in which hormone-permissive tissue injury licenses macrophage-centered inflammatory, fibrotic and neuroimmune programs. This mini review reframes both disorders as related, but not identical, immune-fibrotic conditions and identifies tractable immunopharmacological nodes. We discuss macrophage plasticity, monocyte recruitment, cytokine and chemokine amplification, inflammasome signaling, TGF-β-driven fibrosis, oxidative and metabolic stress, neuroimmune pain signaling and targeted delivery. We argue that non-hormonal therapy should not be developed simply as an alternative to hormonal suppression. Instead, it should be tested as a phenotype-guided strategy that matches dominant immune-fibrotic programs to mechanism-based interventions while preserving reproductive safety. This framework highlights the need for biomarker-informed patient selection, compartment-specific endpoints and early attention to fertility-compatible translational design.